N-acetylprocainamide(NAPA) is a metabolite of procainamide that shows promise of being valuable as an antiarrhythmic drug in its own right. We reported that NAPA is effective in suppressing premature venticular contractions and is well tolerated by patients on a long-term basis. We are encouraged by the fact that three of four patients have received this drug for over 3 years without developing positive antinuclear antibody (ANA) titers. We also reported a patient who had procainamide-induced lupus, then was switched to NAPA therapy with resolution of his arthralgias within 5 weeks and eventual return over 10 months of his elevated ANA titers to normal. Our major research project this past year defined the pharmacokinetics of NAPA in functionally anephric patients and analyzed the pharmacokinetics of its removal by hemodialysis. We critically examined the relationship between flow and clearance terms used in analyzing hemodialysis data. It appears that preferential partitioning of NAPA into red blood cells increases, rather than restricts, its availability for dialysis. We also discovered probable pharmacokinetic correlates of the hemodynamic changes that occur during dialysis and that are likely to limit the effectiveness of dialytic removal of endogenous compounds as well as drugs. Preliminary studies have determined phenytoin protein binding in dogs and in man. We found that phenytoin was 11.8% free in humans and 21.9% free in dogs. This must contribute to the more rapid elimination of phenytoin in dogs, since only free phenytoin is available for hepatic clearance.